Alterations in the regulation of energy and amino acid metabolism are of etiological importance in morbidity and mortality of the burn patients. This project involves integrated studies of in vivo aIterations of the metabolism of the so-called 'conditionally indispensable" amino acids, especially glutamate-glutamine, arginine and the sulfur amino acids. The specific aims are: 1) to evaluate the status of glutamine metabolism, in relation to its role in both glucose and energy substrate metabolism and the maintenance of nitrogen (N) economy. This aim will involve studies, in burn patients and healthy control subjects, designed to assess the consequences of enteral and parenteral glutamine supplementation on splanchnic protein and amino acid metabolism. Studies in a burn rabbit model will include use of a hyperglutaminemic clamp and mass spectrometry, to assess the major fate of glutamine in pathways of carbon and N metabolism. 2) to examine the status and nutritional factors, especially the sulfur amino acids, that affect glutathione (GSH) metabolism in burned patients. This aim will include studies in patients and a series of investigations in the burn animal model. We will determine the roles of the conditionally indispensable amino acid precursors of GSH synthesis (glutamate/glutamine, glycine and cysteine) in the regulation of glutathione metabolism after burn injury. 3) to explore the status of arginine metabolism and the regulatory factors of nitric oxide synthesis after burn injury, in relation to organ function (effect of arginine supply and the metabolic modulation of NO synthesis in different organs, especially lungs, liver and kidneys). This aim will include an initial determination of the significance of asymmetric dimethyl-arginine and homocysteine in the interplay between arginine and NO metabolism, 4) to develop and apply a new mass isotopomer method for determination of albumin synthesis rate and then to adapt this method to assess the synthesis rates of acute phase proteins, including CRP, fibronectin, Apo B 100 and other liver export proteins, at different stages of recovery in burn patients. This research is expected to significantly expand our understanding of the pathophysiology of the N catabolism and how it might be through "designer" nutritional / pharmacological therapy.